Nuclear AGO1 Regulates Gene Expression by Affecting Chromatin Architecture in Human Cells.
Parsi, Krishna Mohan
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Applied Mathematics and Computational Science Program
Computer Science Program
Permanent link to this recordhttp://hdl.handle.net/10754/659968
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AbstractThe impact of mammalian RNA interference components, particularly, Argonaute proteins, on chromatin organization is unexplored. Recent reports indicate that AGO1 association with chromatin appears to influence gene expression. To uncover the role of AGO1 in the nucleus, we used a combination of genome-wide approaches in control and AGO1-depleted HepG2 cells. We found that AGO1 strongly associates with active enhancers and RNA being produced at those sites. Hi-C analysis revealed AGO1 enrichment at the boundaries of topologically associated domains (TADs). By Hi-C in AGO1 knockdown cells, we observed changes in chromatin organization, including TADs and A/B compartment mixing, specifically in AGO1-bound regions. Distinct groups of genes and especially eRNA transcripts located within differentially interacting loci showed altered expression upon AGO1 depletion. Moreover, AGO1 association with enhancers is dependent on eRNA transcription. Collectively, our data suggest that enhancer-associated AGO1 contributes to the fine-tuning of chromatin architecture and gene expression in human cells.
CitationShuaib, M., Parsi, K. M., Thimma, M., Adroub, S. A., Hideya, K., Seridi, L., … Orlando, V. (2019). Nuclear AGO1 Regulates Gene Expression by Affecting Chromatin Architecture in Human Cells. Cell Systems. doi:10.1016/j.cels.2019.09.005
SponsorsM.S. conceived this study, designed and performed experiments, analyzedthe data, and wrote the manuscript with input from all the authors. K.M.P.conceived this study, designed, performed experiments, and analyzed thedata. S.A.A. with M.S. performed Hi-C experiments. M.T. and H.K. performedcomputational analyses of CAGE-seq and ChIP-seq data. L.S. and T.R. per-formed computational analyses of ChIP-seq and CAGE-seq data integration.Y.G. performed computational analyses of RIP-seq and ChIP-seq integration.A.F. contributed in RIP-seq experiments. B.F. helped in western blotting. P.C.and H.K. produced and analyzed the CAGE-seq experiment. V.O. conceivedthis study, designed experiments, and wrote the manuscript.